POST-TRANSLATIONAL MODIFICATION OF THE REPLICATIVE DNA POLYMERASE ALPHA

复制 DNA 聚合酶 α 的翻译后修饰

• 批准号: 8171334
• 负责人: Scott G Kennedy
• 金额: $ 2.21万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171334
• 关键词: Anaphase; Binding; Cell Cycle; Computer Retrieval of Information on Scientific Projects Database; DNA Damage; DNA Polymerase I; DNA Repair; Detection; Functional disorder; Funding; Genomic Instability; Grant; Institution; Lead; Metaphase; Mitosis; Phase; Play; Polymerase; Post-Translational Protein Processing; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; United States National Institutes of Health; Work; Yeasts; response; ubiquitin ligase; yeast two hybrid system

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous work has shown that DNA polymerase alpha (Pol1) is tightly regulated during the cell-cycle, and that altered levels of Pol1 can lead to checkpoint control dysfunction, reduced S-phase DNA damage repair, and genomic instability. These observations suggest that Pol1 may be heavily involved in DNA damage detection during replication, as well as checkpoint control. Very little is known about the role that post-translational modifications play in regulating Pol1 during the cell cycle or in response to DNA damage. A likely possibility is that Pol1 undergoes post-translational modification via ubiquitylation or SUMOylation. In support of this idea is the observation that Pol1 rapidly disappears during the metaphase-anaphase transition during mitosis, suggesting that Pol1 undergoes ubiquitylation that signals its degradation; however, the candidate ubiquitin ligase is currently unknown. Due to the fact that this field is relatively unstudied, we propose to use the yeast two-hybrid screen to help elucidate candidate yeast Pol1 binding partners that may be involved in the regulation of Pol1 during the cell-cycle or DNA damage response.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 先前的工作表明，在细胞周期内，DNA聚合酶α（POL1）受到严格的调节，并且POL1的改变可以导致检查点控制功能障碍，减少S期DNA损伤修复和基因组不稳定。 这些观察结果表明，POL1在复制过程中可能与DNA损伤检测以及检查点控制大量涉及。 关于翻译后修饰在调节细胞周期中或对DNA损伤的响应中所起的作用知之甚少。 一个可能的可能性是POL1通过泛素化或Sumoylation进行翻译后修饰。 为了支持这一想法，观察到有丝分裂过程中的中期 - 解相过程中POL1迅速消失，这表明POL1经历了信号的泛素化，这表明其降解。但是，候选泛素连接酶目前尚不清楚。 由于该领域相对未研究，我们建议使用酵母两杂交筛选来帮助阐明候选酵母菌POL1结合伴侣，这些伴侣可能参与细胞周期或DNA损伤响应期间POL1的调节。